04/2025 journal articles
CUTTING THROUGH THE NOISE: A NARRATIVE REVIEW OF ALZHEIMER\'S DISEASE PLASMA BIOMARKERS FOR ROUTINE CLINICAL USE
M. Schöll, A. Vrillon, T. Ikeuchi, F.C. Quevenco, L. Iaccarino, S.Z. Vasileva-Metodiev, S.C. Burnham, J. Hendrix, S. Epelbaum, H. Zetterberg, S. Palmqvist
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryAs novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic. We focus on plasma phosphorylated(p)-tau, specifically plasma p-tau217, as a robust candidate across both primary and secondary care settings.
Despite the high performance and robustness demonstrated in research, plasma p-tau217, like all plasma biomarkers, can be affected by analytical and pre-analytical variability as well as patient comorbidities, sex, ethnicity, and race. This review also discusses the advantages of the two-point cut-off approach to mitigating these factors, and the challenges raised by the resulting intermediate range measurements, where clinical guidance is still unclear. Further validation of plasma p-tau217 in heterogeneous, real-world cohorts will help to increase confidence in testing and support establishing a standardized approach.
Plasma biomarkers are poised to become a more affordable and less invasive alternative to PET and CSF testing. However, understanding the factors that impact plasma biomarker measurement and interpretation is critical prior to their implementation in routine clinical use.
CITATION:
M. Schöll ; A. Vrillon ; T. Ikeuchi ; F.C. Quevenco ; L. Iaccarino ; S.Z. Vasileva-Metodiev ; S.C. Burnham ; J. Hendrix ; S. Epelbaum ; H. Zetterberg ; S. Palmqvist (2025): Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100056
THE IMPACT OF PRE-ANALYTICAL FACTORS ON PLASMA BIOMARKERS FOR ALZHEIMER\'S DISEASE: THE ASPREE HEALTHY AGEING BIOBANK
Zimu Wu, Michelle M. Mielke, Anne M. Murray, James Phung, Alice Owen, Robyn L. Woods, Danni Li, Jo Wrigglesworth, Joanne Ryan
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: The conditions under which samples were collected, processed, and stored in biobanks may influence Alzheimer's disease (AD) biomarker levels.
OBJECTIVES: This study aims to investigate whether a range of pre-analytical factors influence plasma levels of AD biomarkers.
METHODS: Data were obtained from the ASPREE Healthy Ageing Biobank, a cohort of healthy community-dwelling older individuals aged 70+ years in Australia. Five biomarkers were measured using plasma from 11,868 individuals: phosphorylated-tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid-beta 42 and 40 (Aβ42/Aβ40). Linear regression examined the association between pre-analytical factors and biomarker levels.
RESULTS: Participants were aged 70–96 years, and 54 % were female. The mean storage time for samples was 10.6 years (range: 7.7–13.5). Some significant associations were identified between pre-analytical factors and biomarkers, in particular for p-tau181, but the effect sizes were small. Weak negative associations were found between p-tau181 and the time from venepuncture to laboratory (transport) (β: −0.82, p = 0.03), laboratory processing to frozen storage (β:−1.56, p < 0.001), and total years of storage (β: −0.45, p = 0.007), while a positive association was found with intermediate storage at −20 °C/−30 °C compared to −80 °C (β: 2.24, p = 0.004). Longer fasting time was associated with higher levels of both NfL (β: 0.15, p < 0.001) and GFAP (β: 1.75, p < 0.001).
CONCLUSION: Following standard operating procedures, AD biomarkers can be measured in plasma from biobanks stored for up to 13 years, with minimal impact from long-term storage or other pre-analytical factors.
CITATION:
Zimu Wu ; Michelle M. Mielke ; Anne M. Murray ; James Phung ; Alice Owen ; Robyn L. Woods ; Danni Li ; Jo Wrigglesworth ; Joanne Ryan (2025): The impact of pre-analytical factors on plasma biomarkers for Alzheimer's disease: The ASPREE Healthy Ageing Biobank. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100058
QUALITATIVE RESEARCH AND LITERATURE REVIEW SUPPORT THE INTEGRATED ALZHEIMER\'S DISEASE RATING SCALE (IADRS) CONTENT VALIDITY IN EARLY SYMPTOMATIC AD
Laure Delbecque, Emma Elliott, Sophie Cleanthous, Phoebe Heinrich, Stefan Cano, Alette M. Wessels, Alexandra S. Atkins
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND AND OBJECTIVES: The integrated Alzheimer's Disease Rating Scale (iADRS) is a measure of cognition and daily function used to evaluate treatment effects in Alzheimer's disease (AD) clinical trials. This study aimed to assess the content validity of the iADRS in early symptomatic AD, and to determine whether integrating assessment of cognition and function into a single measure of global disease severity is supported by the patients’ experience.
METHODS: A targeted literature review of qualitative research in AD and qualitative interviews with 25 care partners of individuals with early symptomatic AD were conducted. Interviews started with open-ended concept elicitation exploring the patient experience of AD from the care partner perspective, including how cognitive changes affect daily functioning. This was followed by cognitive debriefing of the ADCS-iADL items. Interview transcripts were analyzed thematically. Concepts extracted from the literature review and interviews were categorized into a conceptual model of patient experience of AD. A concept-to-item mapping exercise was conducted to assess the conceptual coverage of the iADRS.
RESULTS: The literature review comprised sixty articles. Interviews were conducted with care partners of 7 individuals with Mild Cognitive Impairment (MCI)-AD and care partners of 18 individuals with dementia due to AD. The resulting conceptual model incorporated 75 concepts related to AD experience categorized into three overarching domains: Cognition, Daily Function and Other Symptoms/Impacts. Interview findings endorsed the close link between cognition and daily function. Concept-to-item mapping demonstrated all Cognition and Daily function sub-domains within the model were assessed by at least one iADRS item, except Work/Professional, providing supportive evidence that the iADRS covers concepts that reflect the patient experience of early symptomatic AD.
CONCLUSIONS: This study offers a comprehensive conceptualisation of the patient experience of early symptomatic AD and highlights the intrinsic connection between cognition and daily function. The findings endorse the relevance of an integrated assessment of cognition and function and provide strong evidence for the content validity of the iADRS, highlighting its utility as a meaningful clinical outcome assessment (COA) for use as an endpoint in AD.
CITATION:
Laure Delbecque ; Emma Elliott ; Sophie Cleanthous ; Phoebe Heinrich ; Stefan Cano ; Alette M. Wessels ; Alexandra S. Atkins (2025): Qualitative research and literature review support the integrated Alzheimer's Disease Rating Scale (iADRS) content validity in early symptomatic AD. The Journal of Prevention of Alzheimer’s Disease (JPAD).https://doi.org/10.1016/j.tjpad.2025.100101
PATIENT ELIGIBILITY FOR AMYLOID-TARGETING IMMUNOTHERAPIES IN ALZHEIMER\'S DISEASE
Jurij Rosen, Frank Jessen
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Amyloid beta (Aβ) targeting immunotherapies have evolved as promising treatment options for patients with early symptomatic Alzheimer's disease (AD). Understanding how eligibilty criteria impact on the number of patients potentially qualifying for treatment is of high relevance for designing diagnostic workflows in clinical practice and for estimating required ressources and costs.
OBJECTIVES: We aimed at estimating the number of potentially eligible patients for treatment with the Aβ targeting antibodies aducanumab, lecanemab and donanemab in a specialized center real-world sample by the applying the phase 3 clinical trial and the appropriate use recommendations (AUR) inclusion and exclusion criteria to the data set. The post-mortem report was used for defining amyloid positivity and the presence of AD pathology in this study.
DESIGN: Retrospective, descriptive study.
SETTING: The multicenter National Alzheimer‘s Coordinating Center-Uniform Data Set (NACC-UDS) and Neuropathology Data Set (NACCsingle bondNP).
PARTICIPANTS: We included all 3,343 participants of the NACC dataset with available post-mortem pathology reports.
MEASUREMENTS/RESULTS: 887 participants were potential candidates for anti-Aβ immunotherapy as they presented with amnestic mild cognitive impairment or mild dementia and the clinical diagnosis of AD (amnestic AD syndrome). Applying the criterion of amyloid positivity (post mortem report) and the clinical trial inclusion and exclusion criteria to this sample resulted in 83 (9 %), 275 (31 %), and 172 (19 %) participants eligible for treatment with aducanumab, lecanemab, and donanemab, respectively. Applying the criteria of the AUR resulted in 242 (27 %) and 266 (30 %) participants eligible for treatment with aducanumab or lecanemab, respectively. The eligible participant groups for each antibody showed partial, but not full overlap. Co-pathologies were common.
CONCLUSIONS: The number of eligible participants varies between the different antibodies and the selected groups only partly overlap, indicating partly different groups of eligible participants for each antibody. Since not all inclusion and exclusion criteria can be extracted from the NACC-UDS dataset, the real number of eligible patients will be smaller.
CITATION:
Jurij Rosen ; Frank Jessen (2025): Patient eligibility for amyloid-targeting immunotherapies in Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100102
ELIGIBILITY FOR DONANEMAB TRIAL IN A POPULATION-BASED STUDY OF COGNITIVE AGING
Katherine E. Jones, Jeremiah A. Aakre, Anna M. Castillo, Vijay K. Ramanan, Walter K. Kremers, Clifford R. Jack Jr, Prashanthi Vemuri, Christopher G Schwarz, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Jonathan Graff-Radford, Maria Vassilaki
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryThe study aimed to assess eligibility for donanemab phase 3 trial in participants of the Mayo Clinic Study of Aging with mild cognitive impairment (MCI) or mild dementia consistent with Alzheimer's disease (AD) clinical syndrome, positive brain amyloid burden, and available tau PET. There were 817 study participants, 60–85 years old, with MCI or dementia consistent with AD clinical syndrome. Applying the Mini-Mental State Examination criteria (20 to 28) and excluding participants with imaging contraindications reduced the sample to 769; 275 participants had amyloid PET available, of whom 130 had also tau PET at the same visit; 56 participants were amyloid positive, had tau PET available at the same visit, and of those, 27 had evidence of tau pathology measured by 18F-flortaucipir PET imaging. Additional eligibility criteria reduced the eligible participants to 23 % (13 out of 56 participants). Neuroimaging findings, central nervous system exclusions, and history of malignancy were the major exclusions.
CITATION:
Katherine E. Jones ; Jeremiah A. Aakre ; Anna M. Castillo ; Vijay K. Ramanan ; Walter K. Kremers ; Clifford R. Jack Jr ; Prashanthi Vemuri ; Christopher G Schwarz ; Val J. Lowe ; David S. Knopman ; Ronald C. Petersen ; Jonathan Graff-Radford ; Maria Vassilak (2025): Eligibility for donanemab trial in a population-based study of cognitive aging. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100088
REAL-WORLD DATASETS FOR THE INTERNATIONAL REGISTRY FOR ALZHEIMER\'S DISEASE AND OTHER DEMENTIAS (INRAD) AND OTHER REGISTRIES: AN INTERNATIONAL CONSENSUS
Robert Perneczky , David Darby , Giovanni B. Frisoni, Robert Hyde , Takeshi Iwatsubo, Catherine J. Mummery, Kee Hyung Park, Johan van Beek, Wiesje M. van der Flier, Frank Jessen
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Many dementia and Alzheimer's disease (AD) registries operate at local or national levels without standardization or comprehensive real-world data (RWD) collection. This initiative sought to achieve consensus among experts on priority outcomes and measures for clinical practice in caring for patients with symptomatic AD, particularly in the mild cognitive impairment and mild to moderate dementia stages.
OBJECTIVE: The primary aim was to define a minimum dataset (MDS) and extended dataset (EDS) to collect RWD in the new International Registry for AD and Other Dementias (InRAD) and other AD registries. The MDS and EDS focus on informing routine clinical practice, covering relevant comorbidities and safety, and are designed to be easily integrated into existing data capture systems.
METHODS AND RESULTS: An international steering committee (ISC) of AD clinician experts lead the initiative. The first drafts of the MDS and EDS were developed based on a previous global inter-societal Delphi consensus on outcome measures for AD. Based on the ISC discussions, a survey was devised and sent to a wider stakeholder group. The ISC discussed the survey results, resulting in a consensus MDS and EDS covering: patient profile and demographics; lifestyle and anthropometrics; co-morbidities and diagnostics; imaging; treatment; clinical characterization; safety; discontinuation; laboratory tests; patient and care partner outcomes; and interface functionality.
CONCLUSION: By learning from successful examples in other clinical areas, addressing current limitations, and proactively enhancing data quality and analytical rigor, the InRAD registry will be a foundation to contribute to improving patient care and outcomes in neurodegenerative diseases.
CITATION:
Robert Perneczky ; David Darby ; Giovanni B. Frisoni ; Robert Hyde ; Takeshi Iwatsubo ; Catherine J. Mummery ; Kee Hyung Park ; Johan van Beek ; Wiesje M. van der Flier ; Frank Jessen (2025): Real-world datasets for the International Registry for Alzheimer's Disease and Other Dementias (InRAD) and other registries: An international consensus. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100096
LECANEMAB FOR EARLY ALZHEIMER\'S DISEASE: APPROPRIATE USE RECOMMENDATIONS FROM THE FRENCH FEDERATION OF MEMORY CLINICS
Nicolas Villain, Vincent Planche, Matthieu Lilamand, Charlotte Cordonnier, Maria Soto-Martin, Hélène Mollion, Stéphanie Bombois, Julien Delrieu, French Federation of Memory Clinics Work Group on Anti-Amyloid Immunotherapies
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryLecanemab, a monoclonal antibody targeting β-amyloid protofibrils, has shown promising results in a Phase III clinical trial for the treatment of early stages of Alzheimer's disease (AD) and has been approved by the European Medicines Agency. An Early Market Authorization could be submitted to the French regulatory agencies, potentially allowing for the drug's use in clinical practice in France in 2025.
To guide French clinicians in administering lecanemab in a standardized way, the French Federation of Memory Clinics has developed appropriate use recommendations for lecanemab that highlight relevant questions established to ensure an optimal risk-benefit ratio.
The recommendations emphasize that lecanemab treatment requires a comprehensive individualized evaluation of the risk-benefit ratio, which should occur in multidisciplinary meetings. When approved, the guidelines support the use of blood biomarkers, proposing specific cutoffs for patients eligible for lecanemab under restricted conditions. In addition to the European Medicines Agency restrictions in patients on anticoagulants, and APOE4 homozygotes, the guidelines recommend against lecanemab treatment for patients with high amyloid-related hemorrhagic risk such as probable cerebral amyloid angiopathy (Boston criteria v1.5) until further data become available. Additionally, we recommend that MRI monitoring be started before the third infusion to account for early Amyloid Related Imaging Abnormalities (ARIA) occurring on lecanemab. It is recommended to establish a specific clinical care pathway with protocols for patients with ARIA, with trained physicians and radiologists with expertise in neurological emergency and intensive care. Finally, a discontinuation protocol based on dementia severity assessment after 18 months of lecanemab treatment is suggested.
Access to lecanemab requires a personalized biological and genetic diagnosis of AD, which is currently not necessary in most cases. Therefore, the healthcare system must rapidly adjust to new diagnostic procedures and treatment delivery to ensure equal access for all individuals.
CITATION:
Nicolas Villain ; Vincent Planche ; Matthieu Lilamand ; Charlotte Cordonnier ; Maria Soto-Martin ; Hélène Mollion ; Stéphanie Bombois ; Julien Delrieu ; French Federation of Memory Clinics Work Group on Anti-Amyloid Immunotherapies (2025): Lecanemab for early Alzheimer's disease: Appropriate use recommendations from the French federation of memory clinics. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100094
BEHAVIOUR CHANGE TECHNIQUES USED IN INTERVENTIONS TARGETING DEMENTIA RISK FACTORS AMONGST OLDER ADULTS IN RURAL AND REMOTE AREAS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Laura Dodds, Kay Deckers, Celia B. Harris, Joyce Siette
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBehavioural interventions targeting health risk factors within rural areas are often not tailored to effectively address the needs and socio-environmental barriers to access and behaviour change faced by these communities. Little is known about the underlying behaviour change mechanisms that contribute to reducing dementia risk for communities living in regional and rural areas. This systematic review and meta-analysis aimed to summarise the effectiveness of behavioural interventions targeting late-life single modifiable dementia risk factors (physical inactivity, poor diet, social isolation and depression) and the mechanisms used to contribute to behaviour change. Six databases were searched to identify regional and rural behavioural interventions targeting modification of late-life dementia risk behaviours between 2000 and 2024. Behaviour change techniques (BCTs) and outcomes for each intervention were extracted. Where possible, meta-analyses were performed to assess the effectiveness of the behavioural intervention on outcomes related to dementia risk. Out of 42,529 articles, 49 studies were included: 22 on physical inactivity, 6 on poor diet, 9 on social isolation, and 12 on depression. Many BCT categories were applied (M = 14.8, SD = 10), with high use of goals and planning (49/49 interventions; 100 %), shaping knowledge (47/49 interventions; 95.9 %), social support (43/49 interventions; 87.8 %) and comparison of outcomes (38/49 interventions; 77.6 %). Social isolation interventions used the most BCTs (M = 18.3; SD = 8.5), followed by depression (M = 17.6; SD = 10.7), physical inactivity (M = 16.0; SD = 11.5), and poor diet (M = 5.2; SD = 3.1). Although effectiveness was limited across interventions, apart from cognitive behavioural therapy for depression (SMD −0.39, 95 % CI −0.55 to −0.24), future programs targeting dementia risk factors would benefit from incorporation of BCTs. Simultaneously, consideration of the socio-environmental context, accessibility, and community involvement in rural and regional areas may improve the sustainability of interventions.
CITATION:
Laura Dodds ; Kay Deckers ; Celia B. Harris ; Joyce Siette (2025): Behaviour change techniques used in interventions targeting dementia risk factors amongst older adults in rural and remote areas: A systematic review and meta-analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100093
INFLUENCE OF APOE Ε4 ON PERFORMANCE OF CSF BIOMARKERS IN DIFFERENTIATING CLINICAL ALZHEIMER\'S DISEASE
Yan Wang, Fangyu Li, Qi Qin, Tingting Li, Qi Wang, Yan Li, Ying Li, Jianping Jia, Alzheimer\'s Disease Neuroimaging Initiative
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryINTRODUCTION: Apolipoprotein E ε4 (APOE ε4) bring the higher risk of Alzheimer’ Disease (AD). It is essential to evaluate whether the diagnostic performances and critical values of cerebrospinal fluid (CSF) biomarkers are influenced by APOE ε4, which has guiding significance for the clinical practical application.
METHODS: The differences in CSF biomarkers and their performances between APOE ε4 carriers and non-carriers in distinguishing AD, mild cognitive impairment (MCI) and preclinical AD from normal controls (NCs) were analyzed. The receiver operating characteristic (ROC) curves were generated to compare the area under the curve (AUC) between APOE ε4 carriers and non-carriers, as well as the critical values corresponding Youden Index.
RESULTS: In a cross sectional convenience sample of 1610 participants, lower Aβ42 and Aβ42/Aβ40 and higher p-Tau 181/Aβ42 in CSF were observed among APOE ε4 carriers than non-carriers in NC, MCI, and AD groups (P< 0.05). The performance of CSF p-tau/Aβ42 in distinguishing MCI from NC among APOE ε4 carriers was superior to non-carriers [AUC: 0.714 (95%CI: 0.673- 0.752) vs 0.600 (95%CI: 0.564- 0.634), P< 0.001], although it was similar in distinguishing AD from NC between APOE ε4 carriers and non-carriers [AUC: 0.874 (95%CI: 0.835-0.906) vs 0.876 (95%CI: 0.843- 0.904)]. In the longitudinal cohort of 254 participants, the association of CSF Aβ42, Aβ42/Aβ40 and p-Tau181/Aβ42 with cognitive decline were stronger in APOE ε4 carriers compared to non-carriers (P< 0.05). Meanwhile, the critical values were different depending on APOE genotype.
DISCUSSION: The CSF level of p-Tau181/Aβ42 was significantly different between APOE ε4 carriers and non-carriers at different stages of AD. The results indicate that the performances of CSF biomarkers are influenced by APOE ε4, which should be considered in the practical application.
CITATION:
Yan Wang ; Fangyu Li ; Qi Qin ; Tingting Li ; Qi Wang ; Yan Li ; Ying Li ; Jianping Jia ; Alzheimer's Disease Neuroimaging Initiative (2025): Influence of APOE ε4 on performance of CSF biomarkers in differentiating clinical Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100065
ASSESSING THE CAUSAL ROLE OF LIPID METABOLITES IN ALZHEIMER\'S DISEASE: A MENDELIAN RANDOMIZATION STUDY
Haoxiang Hu, Jiesheng Mao, Yunhan Zhao, Yihan Zhang, Yihan Zhang, Jiang hai He, Xiaokai Yang
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: The causal relationship between lipid metabolites and Alzheimer's disease (AD) remains unclear and contradictory. This study aimed to systematically assess the causal relationship between lipid metabolites and AD.
METHODS: A two-step bidirectional Mendelian Randomization (MR) study was employed. The principal analytical technique used to evaluate causation was inverse variance weighting (IVW). Furthermore, mediation analysis was conducted to evaluate the possible function of lipidomes as mediators in the lipid-AD pathway.
RESULTS: Among the 213 lipid metabolites analyzed, significant causal associations with AD were identified Cholesterol esters in large LDL(L-LDL-CE) (OR = 1.236, 95 %CI = 1.052–1.453, P = 0.010), Total cholesterol in large LDL(L-LDL-TC) (OR = 1.506, 95 %CI = 1.235–1.835, P < 0.001), Total cholesterol in medium LDL(M-LDL-TC) (OR = 1.378, 95 %CI = 1.132–1.677, P = 0.001). Mediation analysis further revealed ceramide (d42:2) and phosphatidylinositol (PI) (18:1_18:1) as potential mediators in this relationship.
CONCLUSION: The identification of specific lipid metabolites with causal effects on AD provides new insights into AD pathogenesis and highlights potential targets for preventive strategies.
CITATION:
Haoxiang Hu ; Jiesheng Mao ; Yunhan Zhao ; Yihan Zhang ; Caixiang Zhuang ; Jiang hai He ; Xiaokai Yang (2025): Assessing the causal role of lipid metabolites in Alzheimer's disease: A mendelian randomization study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.10006
CHARACTERIZING AND VALIDATING 12-MONTH RELIABLE COGNITIVE CHANGE IN EARLY-ONSET ALZHEIMER\'S DISEASE FOR USE IN CLINICAL TRIALS
Dustin B. Hammers, Jane Musema, Ani Eloyan, Maryanne Thangarajah, Alexander Taurone, Renaud La Joie, Alexandra Touroutoglou, Prashanthi Vemuri, Joel Kramer, Paul Aisen, Jeffrey L. Dage, Kelly N. Nudelman, Kala Kirby, Alireza Atri, David Clark, Gregory S. Day, Ranjan Duara, Neill R. Graff-Radford, Ian Grant, Lawrence S. Honig, Erik C.B. Johnson, David T. Jones, Joseph C. Masdeu, Mario F. Mendez, Kyle Womack, Erik Musiek, Chiadi U. Onyike, Meghan Riddle, Emily Rogalski, Steven Salloway, Sharon J. Sha, Raymond Scott Turner, Thomas S. Wingo, David A. Wolk, Maria C. Carrillo, Gil D. Rabinovici, Bradford C. Dickerson, Liana G. Apostolova, the LEADS Consortium
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: As literature suggests that Early-Onset Alzheimer's Disease (EOAD) and late-onset AD may differ in important ways, need exists for randomized clinical trials for treatments tailored to EOAD. Accurately measuring reliable cognitive change in individual patients with EOAD will have great value for these trials.
OBJECTIVES: The current study sought to characterize and validate 12-month reliable change from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) neuropsychological battery.
DESIGN: Standardized regression-based (SRB) prediction equations were developed from age-matched cognitively intact participants within LEADS, and applied to clinically impaired participants from LEADS.
SETTING: Participants were recruited from outpatient academic medical centers.
PARTICIPANTS: Participants were enrolled in LEADS and diagnosed with amyloid-positive EOAD (n = 189) and amyloid-negative early-onset cognitive impairment not related to AD (EOnonAD; n = 43).
MEASUREMENT: 12-month reliable change (Z-scores) was compared between groups across cognitive domain composites, and distributions of individual participant trajectories were examined. Prediction of Z-scores by common AD biomarkers was also considered.
RESULTS: Both EOAD and EOnonAD displayed significantly lower 12-month follow-up scores than were predicted based on SRB equations, with declines more pronounced for EOAD across several domains. AD biomarkers of cerebral β-amyloid, tau, and EOAD-specific atrophy were predictive of 12-month change scores.
CONCLUSIONS: The current results support including EOAD patients in longitudinal clinical trials, and generate evidence of validation for using 12-month reliable cognitive change as a clinical outcome metric in clinical trials in EOAD cohorts like LEADS. Doing so will enhance the success of EOAD trials and permit a better understanding of individual responses to treatment.
CITATION:
Dustin B. Hammers ; Jane Musema ; Ani Eloyan ; Maryanne Thangarajah ; Alexander Taurone ; Renaud La Joie ; Alexandra Touroutoglou ; Prashanthi Vemuri ; Joel Kramer ; Paul Aisen ; Jeffrey L. Dage ; Kelly N. Nudelman ; Kala Kirby ; Alireza Atri ; David Clark ; Gregory S. Day ; Ranjan Duara ; Neill R. Graff-Radford ; Ian Grant ; Lawrence S. Honig ; Erik C.B. Johnson ; David T. Jones ; Joseph C. Masdeu ; Mario F. Mendez ; Kyle Womack ; Erik Musiek ; Chiadi U. Onyike ; Meghan Riddle ; Emily Rogalski ; Steven Salloway ; Sharon J. Sha ; Raymond Scott Turner ; Thomas S. Wingo ; David A. Wolk ; Maria C. Carrillo ; Gil D. Rabinovici ; Bradford C. Dickerson ; Liana G. Apostolova ; the LEADS Consortium (2025): Characterizing and validating 12-month reliable cognitive change in Early-Onset Alzheimer's Disease for use in clinical trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100075
FEASIBILITY OF COMPUTERIZED MOTOR, COGNITIVE AND SPEECH TESTS IN THE HOME: ANALYSIS OF TAS TEST IN 2,300 OLDER ADULTS
Guan Huang, Renjie Li, Eddy Roccati, Katherine Lawler, Aidan Bindoff, Anna King, James Vickers, Quan Bai, Jane Alty
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Early detection of Alzheimer's disease (AD) risk is crucial for dementia prevention. Tasmanian Test (TAS Test) is a novel, unsupervised, computerized assessment of motor, cognitive, and speech function designed to detect AD risk.
OBJECTIVES: To evaluate the feasibility, usability, and acceptability of TAS Test.
DESIGN AND SETTING: TAS Test was administered remotely at home and/or in a research facility, using personal computers.
PARTICIPANTS: 2,351 adults aged 50–89 years (mean 65.35), 71.76 % female, from Tasmania, Australia.
MEASUREMENTS: Completion rates, ease-of-use, distraction, test duration, and enjoyment scores. Demographics, computer literacy, cognition, and mood were analyzed.
RESULTS: Over 80 % completed motor and cognitive components with 92.8 % completing speech tests. 89.81 % found the duration acceptable. 80.90 % of remote and 83.46 % of onsite participants enjoyed the procedure. High usability and acceptability were reported, with age, gender, education, computer literacy, cognition and mood having minimal or no impact.
CONCLUSIONS: TAS Test demonstrated high completion rates and user satisfaction across a large community sample, supporting its feasibility as an unsupervised computerized assessment tool. Future research should address demographic representation and technical refinements.
CITATION:
Guan Huang ; Renjie Li ; Eddy Roccati ; Katherine Lawler ; Aidan Bindoff ; Anna King ; James Vickers ; Quan Bai ; Jane Alty (2025): Feasibility of computerized motor, cognitive and speech tests in the home: Analysis of TAS Test in 2,300 older adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100081
BIOFLUID BIOMARKER CHANGES FOLLOWING TREATMENT WITH SABIRNETUG (ACU193) IN INTERCEPT-AD, A PHASE 1 TRIAL IN EARLY ALZHEIMER\'S DISEASE
Erika N. Cline, Daniel Antwi-Berko, Karen Sundell, Elizabeth Johnson, Maddelyn Hyland, Hao Zhang, Hugo Vanderstichele, June Kaplow, Robert A. Dean, Erik Stoops, Eugeen Vanmechelen, Marleen J.A. Koel-Simmelink, Charlotte E. Teunissen, Gopalan Sethuraman, Todd Feaster, Eric Siemers, Jasna Jerecic
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryOBJECTIVE: Sabirnetug (ACU193) is a humanized monoclonal antibody selective for soluble amyloid beta oligomers (AβOs), synaptotoxins that are early and persistent triggers of Alzheimer's disease (AD). Sabirnetug pharmacodynamics were examined in the INTERCEPT-AD phase 1 study in mild cognitive impairment and mild dementia due to AD (NCT04931459) using biofluid biomarkers associated with Aβ and tau pathology, synaptic dysfunction, neuroinflammation, and neurodegeneration.
METHODS: INTERCEPT-AD was a randomized, first-in-human study of sabirnetug versus placebo administered as a single (SAD; 2, 10, 25, 60 mg/kg) or multiple (MAD; three doses of 10 or 60 mg/kg every 4 weeks [Q4W] or 25 mg/kg Q2W) ascending doses. Biomarkers were measured pre-/post-dose in CSF and EDTA-plasma. Correlations of biomarker changes versus dose, exposure duration, and target engagement were determined.
RESULTS: In MAD cohorts, CSF pTau181 decreased significantly (60 mg/kg Q4W, p = 0.049). VAMP2 decreased significantly at all doses (p ≤ 0.041); neurogranin decreased significantly at 60 mg/kg Q4W (p = 0.037). Aβ1-42/Aβ1–40 trended upward with sabirnetug dose. Aβ1–42/Aβ1–40 and neurogranin changes correlated with sabirnetug-AβO target engagement (p ≤ 0.01). Decreases in tTau, VAMP2, and neurogranin correlated with exposure duration (p ≤ 0.007). Plasma pTau181, pTau217, GFAP, and NfL trended lower.
DISCUSSION: Following three sabirnetug doses, changes in CSF and plasma biomarkers were observed. The CSF biomarker response increased with increasing dose and exposure duration, consistent with previous reports that sabirnetug reaches the central compartment and engages its AβO target. The ongoing phase 2 ALTITUDE-AD study (NCT06335173) will test whether sabirnetug's pharmacodynamic effects can be substantiated with a larger sample size and longer treatment duration.
CITATION:
Erika N. Cline ; Daniel Antwi-Berko ; Karen Sundell ; Elizabeth Johnson ; Maddelyn Hyland ; Hao Zhang ; Hugo Vanderstichele ; June Kaplow ; Robert A. Dean ; Erik Stoops ; Eugeen Vanmechelen ; Marleen J.A. Koel-Simmelink ; Charlotte E. Teunissen ; Gopalan Sethuraman ; Todd Feaster ; Eric Siemers ; Jasna Jerecic (2025): Biofluid biomarker changes following treatment with sabirnetug (ACU193) in INTERCEPT-AD, a phase 1 trial in early Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100082
PHYSICAL AND MENTAL DEMANDS OF WORK ASSOCIATED WITH DEMENTIA RISK IN LATER LIFE
Hang-Ju Yang, Yun-Chieh Yang, Chih-Cheng Hsu, Wan-Ju Cheng
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Work occupies a significant portion of adult life, and both cognitive stimulation and physical activity have been suggested as factors that may lower dementia risk in later life.
OBJECTIVES: To examine the association between mental and physical demands at work and the risk of dementia.
DESIGN: A cohort study.
SETTING: Seven selected districts in Taiwan, covering both urban and rural areas.
PARTICIPANTS: 4,083 community-dwelling healthy adults aged 55 and older from the Healthy Aging Longitudinal Study.
MEASUREMENTS: A job matrix of work conditions by occupation was generated using data from a representative national survey. Mental demands were assessed by job control and psychological demands from the Job Content Questionnaire, as well as skill levels. Physical demands were assessed using a 4-point Likert scale and dichotomized into high and low levels. Dementia diagnoses were identified based on physician diagnosis registered in the National Health Insurance database.
RESULTS: Over a follow-up period of 6.2 years, 513 participants were diagnosed with dementia. After adjusting for confounding factors in cox regression models, high (vs. low) job control, high -skilled jobs (vs. low), and high physical demands (vs. low) were associated with a reduced future risk of dementia. Psychological demands were not associated with dementia risk.
CONCLUSIONS: Greater utilization of job skills and engagement in physically demanding activities at work may help mitigate the risk of developing dementia. The effects of different dimensions of psychological demands on cognitive health warrant further investigation.
CITATION:
Hang-Ju Yang ; Yun-Chieh Yang ; Chih-Cheng Hsu ; Wan-Ju Cheng (2025): Physical and mental demands of work associated with dementia risk in later life. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100084
WHITE MATTER HYPERINTENSITY SEVERITY MODIFIES GUT METABOLITE ASSOCIATION WITH COGNITIVE OUTCOMES
Naruchorn Kijpaisalratana, Chia-Ling Phuah, Zsuzsanna Ament, Varun M. Bhave, Ana-Lucia Garcia-Guarniz, Jonathan Duskin, Catharine A. Couch, M. Ryan Irvin, W. Taylor Kimberly, Alzheimer\'s Disease Neuroimaging Initiative, Alzheimer Disease Metabolomics Consortium
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Gut microbiome-associated metabolites and white matter hyperintensities (WMH) are independently associated with cognitive impairment. However, it is unclear if gut metabolites and WMH interact to influence dementia.
OBJECTIVES: To examine the association between gut microbial metabolites and cognitive outcomes and assess whether the severity of baseline WMH would impact associations between gut microbial metabolites and cognitive outcomes.
DESIGN: Cross-sectional design. Setting: Cohort of individuals who are clinically normal, mild cognitive impairment, or Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants: A total of 578 participants with available baseline 3.0T 2D-Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) scans and baseline gut microbial metabolite measurement were included in the analysis.
MEASUREMENTS: Gut metabolite measurements and automated WMH volume estimations were obtained from FLAIR MRI and were used to assess the association and interaction with cognitive impairment.
RESULTS: Of 104 metabolites studied, glycodeoxycholic acid (GDCA) surpassed the false discovery rate and was associated the Alzheimer's Disease Assessment Scale-Cognitive Subscale version 13 (ADAS-Cog13) score (β = 0.12, 95 % CI = 0.05–0.20, p = 0.001) and cognitive impairment determined by mini-mental status exam (MMSE) (OR = 2.11, 95 % CI = 1.41–3.15, p < 0.001). GDCA was associated with higher ADAS-Cog13 in participants with low WMH burden (β = 0.21, 95% CI = 0.10–0.32, p < 0.001) but not in participants with high WMH burden (β = 0.04, 95 % CI = -0.07 to 0.14, p = 0.48; interaction p = 0.02).
CONCLUSION: An elevated level of GDCA was associated with worse cognition. WMH severity modified the association between GDCA and cognitive outcomes.
CITATION:
Naruchorn Kijpaisalratana ; Chia-Ling Phuah ; Zsuzsanna Ament ; Varun M. Bhave ; Ana-Lucia Garcia-Guarniz ; Jonathan Duskin ; Catharine A. Couch ; M. Ryan Irvin ; W. Taylor Kimberly ; Alzheimer's Disease Neuroimaging Initiative ; Alzheimer Disease Metabolomics Consortium (2025): White matter hyperintensity severity modifies gut metabolite association with cognitive outcomes. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100086
ASSOCIATION BETWEEN L-Α GLYCERYLPHOSPHORYLCHOLINE USE AND DELAYED DEMENTIA CONVERSION: A NATIONWIDE LONGITUDINAL STUDY IN SOUTH KOREA
Han-Kyeol Kim, Sojeong Park, Sung-Woo Kim, Eun Seok Park, Jin Yong Hong, Ickpyo Hong, Min Seok Baek
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Alzheimer's disease and vascular dementia are two of the most common causes of dementia. While early diagnosis and intervention are crucial, available treatments and research concerning the mild cognitive impairment stage remain limited. This study aimed to evaluate the real-world effectiveness and safety of L-α glycerylphosphorylcholine in this context.
OBJECTIVES: To investigate the impact of L-α glycerylphosphorylcholine on the risk of conversion from mild cognitive impairment to Alzheimer's disease dementia and vascular dementia, as well as its influence on stroke risk.
DESIGN: A nationwide, population-based cohort study.
SETTING: Data from South Korea's National Health Insurance Service.
PARTICIPANTS: Overall, 508,107 patients newly diagnosed with mild cognitive impairment between 2013 and 2016 were included.
INTERVENTION: Patients were classified as users or non-users of L-α glycerylphosphorylcholine based on prescription records.
MEASUREMENTS: The primary outcomes were the risk of progression to Alzheimer's disease dementia and vascular dementia. Stroke risk was examined as a secondary outcome. A time-dependent Cox regression analysis was used to adjust for demographic and clinical factors.
RESULTS: Compared to non-users, L-α glycerylphosphorylcholine users had a lower risk of progression to Alzheimer's disease dementia (hazard ratio = 0.899, 95 % confidence interval: 0.882–0.918) and vascular dementia (hazard ratio = 0.832, 95 % confidence interval: 0.801–0.865) within 2,435,924 and 662,281.6 person-years, respectively. In patients under 65, L-α glycerylphosphorylcholine significantly reduced the risk of progression to Alzheimer's and vascular dementia. Stroke risk significantly decreased in patients who did not progress to dementia but not in those who did.
CONCLUSIONS: L-α Glycerylphosphorylcholine reduces dementia conversion and stroke risk in patients with mild cognitive impairment, making it a viable early intervention. Future large-scale randomized controlled studies should examine its effects on other dementia subtypes and long-term cognitive outcomes.
CITATION:
Han-Kyeol Kim ; Sojeong Park ; Sung-Woo Kim ; Eun Seok Park ; Jin Yong Hong ; Ickpyo Hong ; Min Seok Baek (2025): Association between L-α glycerylphosphorylcholine use and delayed dementia conversion: A nationwide longitudinal study in South Korea. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100059
EFFECTS OF TRADITIONAL THAI FOLK DANCE COMBINED WITH COGNITIVE STIMULATION PROGRAM ON BEHAVIOR AND COGNITION AMONG OLDER ADULTS WITH COGNITIVE DECLINE: A RANDOMIZED CONTROLLED TRIAL
Panawat Sanprakhon, Wachira Suriyawong, Natsala Longphasuk, Natsuda Khatichop, Churai Arpaichiraratana, Sresuda Wongwiseskul, Peerayut Rattanaselanon, Noppamas Pipatpiboon, Papan Thaipisuttikul
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Older adults with mild behavioral impairment (MBI) are at the higher risk of developing dementia compared to those without MBI, leading to decreased quality of life (QoL). Addressing MBI in older adults provides valuable opportunities to prevent dementia.
OBJECTIVES: This study aimed to determine the effects of traditional Thai folk dance combined with a cognitive stimulation program on MBI, QoL, subjective cognitive decline (SCD), and cognitive functioning in older Thai adults.
DESIGN: Single-blinded, two-armed, randomized controlled trial, with a three-month follow-up period.
SETTING: Outpatient chronic disease clinics at two districts in Suphan Buri province, Thailand.
PARTICIPANTS: One-hundred twenty-eight older adults with MBI were randomly assigned to either the experimental (n = 64) and cognitive education control group (n = 64).
INTERVENTION: The 14-session, 7-week traditional Thai folk-dance program combined with cognitive stimulation focused on enhanced moderate intensity physical activity and cognitive stimulation engagement to improve MBI of older adults.
MEASUREMENTS: The primary outcome was MBI assessed using Mild Behavioral Impairment Checklist. Secondary outcomes were QoL, SCD, and cognitive tests of memory and executive functions.
RESULTS: Compared to the control group, participants in the experimental group demonstrated significantly reduced MBI (p <.01), improved QoL (p <.01), decreased SCD (p <.01), and enhanced cognitive functioning (p <.01) after the 7-week intervention and at the 12-week follow-up.
CONCLUSION: The traditional Thai folk dance combined with cognitive stimulation improved outcomes related to early signs of dementia and enhanced the overall QoL of older adults.
CITATION:
Panawat Sanprakhon ; Wachira Suriyawong ; Natsala Longphasuk ; Natsuda Khatichop ; Churai Arpaichiraratana ; Sresuda Wongwiseskul ; Peerayut Rattanaselanon ; Noppamas Pipatpiboon ; Papan Thaipisuttikul (2025): Effects of traditional Thai folk dance combined with cognitive stimulation program on behavior and cognition among older adults with cognitive decline: A randomized controlled trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100066
A POINT-BASED COGNITIVE IMPAIRMENT SCORING SYSTEM FOR SOUTHEAST ASIAN ADULTS
Wei Ying Tan, Xiangyuan Huang, Caroline Robert, Mervin Tee, Christopher Chen, Gerald Choon Huat Koh, Rob M. van Dam, Nagaendran Kandiah, Saima Hilal
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Cognitive impairment is a growing concern in Southeast Asian populations, where the burden of cerebrovascular disease (CeVD) is high. Currently, there is no point-based scoring system for identifying cognitive impairment in these populations.
OBJECTIVE: To develop and validate a simple point-based Cognitive Impairment Scoring System (CISS) for identifying individuals with cognitive impairment no dementia (CIND) and concomitant CeVD in Southeast Asian populations.
DESIGN: A cross-sectional study using data from two population-based studies.
SETTING: Community-based setting in Southeast Asia.
PARTICIPANTS: 1,511 Southeast Asian adults (664 with CIND, 44.0 %).
MEASURES: Two CISS measures were developed: a basic measure including 11 easily assessable risk factors, and an extended measure incorporating seven additional neuroimaging markers. Performance was evaluated using receiver operating characteristic analysis (AUC) and calibration plots.
RESULTS: The AUC for CISS-basic and CISS-extended were 0.81 (95 %CI, 0.76–0.86) and 0.85 (95 %CI, 0.81–0.89), respectively. Calibration plots indicated satisfactory fit for both the basic measure (p=0.82) and the extended measure (p=0.17). The basic measure included age, gender, ethnicity, education, systolic blood pressure, BMI, smoking history, diabetes, hyperlipidemia, stroke history, and mild/moderate depression. The extended measure added neuroimaging markers of CeVD and brain atrophy.
CONCLUSION: The CISS provides a quick, objective, and clinically relevant tool for assessing cognitive impairment risk in Southeast Asian populations. The basic measure is suitable for initial community-based screenings, while the extended measure offers higher specificity for probable diagnosis. This point-based system enables rapid estimation of cognitive status without requiring complex calculations, potentially improving early detection and management of cognitive impairment in clinical practice.
CITATION:
Wei Ying Tan ; Xiangyuan Huang ; Caroline Robert ; Mervin Tee ; Christopher Chen ; Gerald Choon Huat Koh ; Rob M. van Dam ; Nagaendran Kandiah ; Saima Hilal (2025): A point-based cognitive impairment scoring system for southeast Asian adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100069
ASSOCIATION OF DIETARY DIVERSITY, GENETIC SUSCEPTIBILITY, AND THE RISK OF INCIDENT DEMENTIA: A PROSPECTIVE COHORT STUDY
Boyue Zhao, Bolun Cheng, Xinyang Li, Jinyu Xia, Yifan Gou, Meijuan Kang, Jingni Hui, Ye Liu, Ruixue Zhou, Chen Liu, Bingyi Wang, Panxing Shi, Feng Zhang
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryBACKGROUND: Previous studies have revealed how single foods or nutrients affect dementia, but the evidence for a potential link between dietary diversity and dementia is inconsistent.
OBJECTIVES: This study aimed to evaluate the association between dietary diversity and the risk of incident dementia.
DESIGN, SETTING AND PARTICIPANTS : This prospective study included 104,572 white participants without dementia at baseline recruited between 2006 and 2010 from the UK Biobank.
MEASUREMENTS: Dietary Diversity Score (DDS) was acquired through the Oxford WebQ's 24-hour dietary recall survey spanning from 2009 to 2012. Cox proportional hazards models were used to estimate the associations between DDS, diversity scores of food groups and the risk of incident dementia. Stratified analyses were subsequently conducted to assess the potential variations across different demographic, socioeconomic, and genetic risk groups.
RESULTS: Over a median follow-up period of 10.44 years, 725 participants developed incident dementia. A higher DDS was associated with a lower risk of incident dementia (HR: 0.95; 95 % CI: 0.93–0.97). Stratified analyses revealed statistical significance in this association for individuals under 65 years old (HR: 0.95; 95 % CI: 0.92–0.98), and those with higher polygenic risk scores (PRS; HR: 0.92; 95 % CI: 0.89–0.95). Among five food groups, a higher diversity score for meat and protein alternatives was associated with a lower risk of dementia (HR: 0.92; 95 % CI: 0.86–0.99).
CONCLUSION: Enhancing dietary diversity reduces dementia risk, and is potentially influenced by genetic predisposition. Consuming a diverse range of foods may be an effective strategy against dementia.
CITATION:
Boyue Zhao ; Bolun Cheng ; Xinyang Li ; Jinyu Xia ; Yifan Gou ; Meijuan Kang ; Jingni Hui ; Ye Liu ; Ruixue Zhou ; Chen Liu ; Bingyi Wang ; Panxing Shi ; Feng Zhang (2025): Association of dietary diversity, genetic susceptibility, and the risk of incident dementia: A prospective cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100078
JOINT ENSEMBLE LEARNING-BASED RISK PREDICTION OF ALZHEIMER\'S DISEASE AMONG MILD COGNITIVE IMPAIRMENT PATIENTS
Tianyuan Guan, Lei Shang, Peng Yang, Zhijun Tan, Yue Liu, Chunling Dong, Xueying Li, Zuxuan Hu, Haixia Su, Yuhai Zhang
J Prev Alz Dis 2025;4(12)
Show summaryHide summaryOBJECTIVE: Due to the recognition for the importance of early intervention in Alzheimer's disease (AD), it is important to focus on prevention and treatment strategies for mild cognitive impairment (MCI). This study aimed to establish a risk prediction model for AD among MCI patients to provide clinical guidance for primary medical institutions.
METHODS: Data from MCI subjects were obtained from the NACC. Importance ranking and the SHapley Additive exPlanations (SHAP) method for the Random Survival Forest (RSF) and Extreme Gradient Boosting (XGBoost) algorithms in ensemble learning were adopted to select the predictors, and hierarchical clustering analysis was used to mitigate multicollinearity. The RSF, XGBoost and Cox proportional hazard regression (Cox) models were established to predict the risk of AD among MCI patients. Additionally, the effects of the three models were evaluated.
RESULTS: A total of 3674 subjects with MCI were included. Thirteen predictors were ultimately identified. In the validation set, the concordance indices were 0.781 (RSF), 0.781 (XGBoost), and 0.798 (Cox), and the Integrated Brier Score was 0.087 (Cox). The prediction effects of the XGBoost and RSF models were not better than those of the Cox model.
CONCLUSION: The ensemble learning method can effectively select predictors of AD risk among MCI subjects. The Cox proportional hazards regression model could be used in primary medical institutions to rapidly screen for the risk of AD among MCI patients once the model is fully clinically validated. The predictors were easy to explain and obtain, and the prediction of AD was accurate.
CITATION:
Tianyuan Guan ; Lei Shang ; Peng Yang ; Zhijun Tan ; Yue Liu ; Chunling Dong ; Xueying Li ; Zuxuan Hu ; Haixia Su ; Yuhai Zhang (2025): Joint ensemble learning-based risk prediction of Alzheimer's disease among mild cognitive impairment patients. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100083
LETTER TO THE EDITOR: REEVALUATING THE SLEEP-DEMENTIA LINK: METHODOLOGICAL GAPS AND FUTURE DIRECTIONS
Julián Benito-León, Carla María Benito-Rodríguez
J Prev Alz Dis 2025;4(12)
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CITATION:
Julián Benito-León ; Carla María Benito-Rodríguez (2025): Letter to the Editor: Reevaluating the sleep-dementia link: Methodological gaps and future directions. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100085
LETTER TO THE EDITOR: MITOCHONDRIAL DYSFUNCTION AS THE MISSING LINK BETWEEN CIRCADIAN SYNDROME AND DEMENTIA
Yu-Hsiang Lin, Kuo-Jen Lin, Po-Ting Lin
J Prev Alz Dis 2025;4(12)
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CITATION:
Yu-Hsiang Lin ; Kuo-Jen Lin ; Po-Ting Lin (2025): Letter to the Editor: Mitochondrial dysfunction as the missing link between circadian syndrome and dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100125
REPLY TO THE LETTER TO THE EDITOR: MITOCHONDRIAL DYSFUNCTION AS THE MISSING LINK BETWEEN CIRCADIAN SYNDROME AND DEMENTIA
Linling Yu, Xiong Wang
J Prev Alz Dis 2025;4(12)
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CITATION:
Linling Yu ; Xiong Wang (2025): Reply to the Letter to the Editor: Mitochondrial dysfunction as the missing link between circadian syndrome and dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100126
CORRIGENDUM TO “17TH CLINICAL TRIALS ON ALZHEIMER\'S DISEASE (CTAD) MADRID, SPAIN, OCTOBER 29 - NOVEMBER 1, 2024: SYMPOSIA, ORAL COMMUNICATIONS” [J PREV ALZHEIMERS DIS 2025;12(1S):100043].
J Prev Alz Dis 2025;4(12)
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